A process for the preparation of 3-bromo-3-alkyl-2,2-difluoropropionic acid ethyl ester and coumarin / quinoxalinone / indole conjugates and antitumor applications

Abstract

The application relates to a method for 3-bromo-3-alkyl-2,2-difluoropropionic acid ethyl ester and coumarin / quinolinone / indole coupling and anti-tumor application, which is prepared from 3-bromo-3-alkyl-2,2-difluoropropionic acid ethyl ester, mixed with formula B at room temperature, added with DMSO as a solvent, selected with an organic amine as a base, and obtained from compound C under light conditions with high yield; a specific reaction formula is as follows: the method has the advantages of good functional group applicability, a simple, green and economical reaction system, and some compounds C have very significant anti-tumor activity.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry application technology, specifically to a method for coupling ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with coumarin / quinolinone / indole and its antitumor application. Background Technology

[0002] Ethyl difluoroacetate is a very important fluorine-containing group, mainly used in pharmaceuticals, pesticides, organic synthesis, and other fields, and has a very important application in medicinal chemistry. On the other hand, heterocyclic compounds such as coumarin / quinolinone are also the core structure of many drugs. Introducing other functional groups into the coumarin and quinolinone rings can enrich the pharmacological properties of these molecules. Currently, existing technology has not found a method for coupling ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with coumarin, quinolinone, indoles, or other compounds with similar structures. Summary of the Invention

[0003] To address the shortcomings of existing technologies, this invention provides a method for coupling ethyl difluoropropionate with coumarin / quinolinone / indole, with the aim of obtaining new compounds with significant antitumor activity through this method.

[0004] One objective of this invention is to provide a method for coupling ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with coumarin / quinolinone / indole. The method involves using ethyl 3-bromo-3-alkyl-2,2-difluoropropionate of formula A as a starting material, mixing it with a compound of formula B at room temperature, adding DMSO as a solvent, and using an organic amine as a base under light irradiation to obtain compound C in high yield. The specific reaction formula is as follows:

[0005]

[0006] In the above formulas, R1 is selected from C1-12 alkyl, phenyl and alkyl or halogen-substituted phenyl groups, and R2 is selected from H, C1-6 alkyl, phenyl, alkenyl, ether, ester, carbonyl, hydroxyl or halogen substituents.

[0007] Furthermore, the molar ratio of compound A to compound B is 1:1 to 10.

[0008] Furthermore, the molar ratio of compound A to the base is 1:2.

[0009] Furthermore, the reaction is carried out at 20℃~50℃.

[0010] Furthermore, the light source is selected from violet light.

[0011] Furthermore, the base is selected from 4-dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, N,N-diisopropylethylamine.

[0012] A second objective of this invention is to provide a compound synthesized by the above method, compound C, as shown below:

[0013]

[0014] The third objective of this invention is to provide the application of compound C in the preparation of antitumor drugs.

[0015] Furthermore, the tumors include liver cancer and lung cancer.

[0016] Working principle: In this invention, the inventors developed a method for coupling ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with coumarin, quinolinone, and indole under photoinduction, using ethyl 3-bromo-3-alkyl-2,2-difluoropropionate as a starting material. Specifically, ethyl 3-bromo-3-alkyl-2,2-difluoropropionate compound A is used as a starting material, and at room temperature, commercially available 4-dimethylaminopyridine is used as a base to react with coumarin, quinolinone, and indole B to obtain compounds containing ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with various structures.

[0017] Beneficial effects: (1) The raw materials used in this method are from industrial raw materials, and the reaction conditions are mild, economical, green and environmentally friendly; (2) The reaction system is simple and homogeneous, which is suitable for large-scale production; (3) The reaction has excellent functional group compatibility and reaction diversity; (4) The synthesis method can obtain new compound structures of coumarin, quinolinone and indole with potential application value, which have potential application value in medicine, pesticide and materials science. Detailed Implementation

[0018] The following detailed description illustrates the specific implementation method:

[0019] This invention provides a simple method for coupling ethyl 3-bromo-3-alkyl-2,2-difluoropropionate with coumarin, quinolinone, and indole. Specifically, the method uses ethyl 3-bromo-3-alkyl-2,2-difluoropropionate A as a raw material, mixes it with coumarin, quinolinone, and indole B at room temperature, adds DMSO as a solvent, and selects an inexpensive and readily available organic amine as a base to obtain compound C in high yield under light conditions.

[0020]

[0021] In the above formulas, R1 is a C1-12 alkyl, phenyl, or alkyl- or halogen-substituted phenyl group, and R2 is H, C1-6 alkyl, phenyl, alkenyl, etheryl, esteryl, carbonyl, hydroxyl, or halogen-substituted group.

[0022] Compounds of Formula A, Formula B, and Formula C of this invention can be prepared by commercially available methods or methods well known to those skilled in the art to which this invention pertains. However, the specific conditions of such methods, such as reactants, solvents, amounts of compounds used, reaction temperatures, and reaction times, are not limited to the explanations below.

[0023] The base can be selected from those well known to those skilled in the art, such as 4-dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, and N,N-diisopropylethylamine.

[0024] In this reaction system, the base used is 200% of the molar amount of compound A.

[0025] The solvent is preferably dimethyl sulfoxide.

[0026] The product obtained by the preparation method of this invention can be separated and purified by various methods, including thin-layer chromatography and column chromatography. These purification methods are all conventional methods in the art. For example, when using thin-layer chromatography and column chromatography, the developing solvent can be a single solvent or a mixed solvent, such as petroleum ether or a mixture of petroleum ether and ethyl acetate.

[0027] The features mentioned above in this invention, or the features mentioned in the embodiments, can be combined arbitrarily. All features disclosed in this specification can be used in any compositional form, and each feature disclosed in the specification can be replaced by any alternative feature that provides the same, equivalent, or similar purpose. Therefore, unless otherwise specified, the disclosed features are merely general examples of equivalent or similar features.

[0028] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0029] In the following examples, purification was performed using conventional post-processing methods in the art.

[0030] Examples 1-3

[0031]

[0032] To a 25 mL reaction tube, add 116.9 mg (0.8 mmol, 4 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine. After purging with argon three times, add 1.0 mL of the corresponding solvent from the table below and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1. Irradiate with ultraviolet light (410–415 nm) and stir at 30 °C for 12 h to obtain compound C-1. The yields are as follows (fluorine spectrum yields). mp: 88–90 °C. 1 H NMR (400MHz, CDCl3) δ7.74(s,1H),7.56–7.52(m,1H),7.49(dd,J=8.0Hz,J=1.6Hz,1H),7.34–7.28(m,2H),7.03(d,J=8.4Hz,2H),6.77(d,J=8.8H z,2H),4.24(q,J=7.2Hz,2H),4.02–3.90(m,1H),3.72(s,3H),2.59(t,J= 7.8Hz,2H),2.32–2.24(m,1H),2.15–2.04(m,1H),1.25(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4 (t, J = 32.9Hz), 161.4, 158.0, 153.2, 141.8, 132.7, 132.0, 129.2, 128.1, 124.6, 123 .6(d,J=5.6Hz),118.9,116.5,115.7(t,J=256.3Hz),113.9,63.2,55.2,42.0(t,J=22.9Hz),32.1,29.8,13.8. 19 F NMR (376MHz, CDCl3) δ-108.27 (dd, J=253.8Hz, J=13.9Hz, 1F), -111.21 (dd, J=253.8Hz, J=18.4Hz, 1F). HRMS (ESI): calculated for C 23 H 23 O5F2([M+H) + ):417.1508; Found:417.1506.C-1 is a new compound.

[0033]

[0034] Examples 4-6

[0035]

[0036] Add 116.9 mg (0.8 mmol, 4 equiv) of B-1 to a 25 mL reaction tube. After purging with argon three times, add DMSO (1.0 mL) and the corresponding electron donors in the table below, and then add 70.2 mg (0.2 mmol, 1 equiv) of compound A-1.

[0037] Compound C-1 was obtained after stirring at 30°C for 12 h under ultraviolet light (410-415 nm) irradiation, with the following yields (fluorine spectrum yields).

[0038]

[0039] Examples 7-8

[0040]

[0041] To a 25 mL reaction tube, 116.9 mg (0.8 mmol, 4 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. Under the corresponding LED irradiation shown in the table below, the mixture was stirred at 30 °C for 12 h to obtain compound C-1, with the following yields (fluorine spectrum yields).

[0042]

[0043] Examples 9-11

[0044]

[0045] To a 25 mL reaction tube, add the corresponding amounts of B-1 (as shown in the table below), 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine, purged three times with argon gas, and then add 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1. After stirring at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation, compound C-1 is obtained, with the following yields (fluorine spectrum yields, with the separated yield in parentheses). Under optimal conditions, the coumarin recovery yield is 71%.

[0046]

[0047] Example 12

[0048]

[0049] To a 25 mL reaction tube, 256.3 mg (1.6 mmol, 8 equiv) of B-2 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410–415 nm) irradiation to give compound C-2 with a yield of 77%. B-2 was recovered in 76% yield. mp: 70–72 °C 1 H NMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.35 (dd, J = 8.4Hz, J = 2.0Hz, 1H), 7.29 (s, 1H), 7.23 (d, J = 8.4Hz, 1H), 7.03 (d, J = 8.4Hz, 2H), 6.77 (d, J = 8.4Hz, 2H), 4 .24(q,J=7.2Hz,2H),4.01–3.89(m,1H),3.74(s,3H),2.57(t,J=7.8Hz,2H) ,2.41(s,3H),2.31–2.23(m,1H),2.13–2.03(m,1H),1.25(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.5 (t, J = 32.8Hz), 161.7, 158.1, 151.4, 141.9, 134.5, 133.1, 132.8, 129.3, 128.0, 123.5 (d,J=5.4Hz),118.7,116.4,115.8(t,J=256.0Hz),114.0,63.3,55.3,42.1(t,J=22.9Hz),32.2,30.0,20.9,13.9. 19 F NMR (376MHz, CDCl3) δ-108.17 (dd, J=253.8Hz, J=13.5Hz, 1F), -111.35 (dd, J=253.8Hz, J=18.4Hz, 1F). HRMS (ESI): calculated forC 24 H 25 O5F2([M+H) + ):431.1665; Found:431.1664.C-2 is a new compound.

[0050] Example 13

[0051]

[0052] To a 25 mL reaction tube, 256.3 mg (1.6 mmol, 8 equiv) of B-3 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410–415 nm) irradiation to give compound C-3 with a yield of 67%. B-3 was recovered in 82% yield. mp: 69–71 °C 1 H NMR (400MHz, CDCl3) δ7.70(s,1H),7.37(d,J=7.6Hz,1H),7.13-7.10(m,2H),7.03(d,J=8.8Hz,2H),6.77(d,J=8.4Hz,2H),4.23(q,J=7.2 Hz,2H),4.00–3.88(m,1H),3.73(s,3H),2.58(t,J=7.8Hz,2H),2.46(s,3H),2.31–2.22(m,1H),2.13–2.03(m,1H),1.24(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.5 (t, J = 32.4Hz), 161.8, 158.1, 153.4, 143.5, 141.9, 132.9, 129.3, 127.9, 125.9, 122.3 (d, J = 5.8Hz) ,116.7(d,J=2.4Hz),116.6,115.9(t,J=255.9Hz),114.0,63.2,55.3(d,J=4.0Hz),42.0(t,J=22.8Hz),32.2,29.9,21.9,13.9. 19 F NMR (376MHz, CDCl3) δ-108.08 (dd, J=253.4Hz, J=13.9Hz, 1F), -111.45 (dd, J=253.4Hz, J=19.2Hz, 1F). HRMS (ESI): calculated forC 24 H 25 O5F2([M+H) + ):431.1665; Found:431.1666.C-3 is a new compound.

[0053] Example 14

[0054]

[0055] To a 25 mL reaction tube, 355.6 mg (1.6 mmol, 8 equiv) of B-4 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-4 with a yield of 79%, while B-4 was recovered in 87% yield. 1 H NMR (400MHz, CDCl3) δ7.81 (s, 1H), 7.76 (dd, J = 8.8Hz, J = 2.4Hz, 1H), 7.68 (d, J = 2.0Hz ,1H),7.59(d,J=7.6Hz,2H),7.49(t,J=7.6Hz,2H),7.42–7.39(m,2H),7.05(d,J=8.4 Hz,2H),6.78(d,J=8.8Hz,2H),4.27(q,J=7.2Hz,2H),4.07–3.95(m,1H),3.72(s,3H) ,2.62(t,J=7.8Hz,2H),2.36–2.28(m,1H),2.20–2.10(m,1H),1.28(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4 (t, J = 32.8Hz), 161.4, 158.1, 152.6, 141.9, 139.4, 138.0, 132. 7,130.9,129.3(d,J=12.6Hz),129.2–129.1(m),128.0–127.8(m),127.1(d,J=3.2Hz),126 .4(d,J=6.1Hz),124.0(d,J=5.3Hz),119.1,116.9(d,J=11.1Hz),115.8(t,J=256.2Hz),11 3.9(d,J=5.2Hz),63.3,55.3(d,J=12.6Hz),42.4–41.8(m),32.2,29.9,13.9(d,J=6.2Hz). 19 F NMR (376MHz, CDCl3) δ-107.97 (d, J=252.3Hz, 1F), -110.87 (d, J=253.0Hz, 1F). HRMS (ESI): calculated for C 29 H 27 O5F2([M+H) + ):493.1821; Found:493.1819.C-4 is a new compound.

[0056] Example 15

[0057]

[0058] To a 25 mL reaction tube, 360.1 mg (1.6 mmol, 8 equiv) of B-5 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation to give compound C-5 with a yield of 54%, and B-5 was recovered in 67% yield. mp: 103–105 °C 1 H NMR (400MHz, CDCl3) δ7.63–7.61(m,3H),7.21(d,J=9.2Hz,1H),7.01(d,J=8.4Hz,2H),6.76(d,J=8.8Hz,2H),4.24(q,J=7. 2Hz,2H),4.00–3.88(m,1H),3.72(s,3H),2.63–2.52(m,2H),2.31–2.23(m,1H),2.13–2.03(m,1H),1.26(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.3(t,J=32.8Hz),160.9,158.2,152.1,140.5,134.7,132.6,130.5,129.3,125.1(d,J=5.1H z),120.5,118.4,117.3,115.6(t,J=257.0Hz),114.0,63.4,55.3(d,J=3.8Hz),42.2(t,J=24.3Hz),32.2,29.9,13.9. 19 F NMR (376MHz, CDCl3) δ-109.20 (d, J=254.5Hz, 1F), -111.39 (d, J=257.2Hz, 1F). HRMS (ESI): calculated for C 23 H 22 O5BrF2([M+H) + ):495.0613; Found:495.0612.C-5 is a new compound.

[0059] Example 16

[0060]

[0061] To a 25 mL reaction tube, 259.4 mg (1.6 mmol, 8 equiv) of B-6 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation to give compound C-6 in 81% yield, with 78% recovery of B-6. mp: 134–136 °C. 1 H NMR (400MHz, CDCl3) δ8.29 (s, 1H), 7.73 (s, 1H), 7.34 (d, J = 8.4Hz, 1H), 7.03 ( d,J=8.4Hz,2H),6.92(d,J=2.4Hz,1H),6.84(dd,J=8.4Hz,J=2.4Hz,1H),6.7 7(d,J=8.4Hz,2H),4.27(q,J=7.1Hz,2H),3.96–3.83(m,1H),3.72(s,3H),2. 61-2.56(m,2H),2.33–2.24(m,1H),2.17–2.06(m,1H),1.27(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ164.1 (t, J = 32.8Hz), 163.1, 160.9 (d, J = 2.7Hz)), 158.0 ,154.8,143.2,132.8,129.6(d,J=4.9Hz),129.3(d,J=14.2Hz),118.4(d,J=4. 7Hz), 115.9 (t, J = 255.8Hz), 114.1, 114.0 (d, J = 6.5Hz), 112.3, 102.8 (d, J = 14. 3Hz), 63.5, 55.3 (d, J = 13.8Hz), 42.2–41.6 (m), 32.1, 29.5, 13.8 (d, J = 7.0Hz). 19 F NMR (376MHz, CDCl3) δ-108.22 (dd, J=251.9Hz, J=12.8Hz, 1F), -111.89 (dd, J=251.9Hz, J=19.6Hz, 1F). HRMS (ESI): calculated for C 23 H 23 O6F2([M+H) + ):433.1457; Found:433.1456.C-6 is a new compound.

[0062] Example 17

[0063]

[0064] To a 25 mL reaction tube, 281.9 mg (1.6 mmol, 8 equiv) of B-7 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-7 with a yield of 67%, and B-7 was recovered in 63% yield. 1 H NMR (400MHz, CDCl3) δ7.68 (s, 1H), 7.38 (d, J = 8.4Hz, 1H), 7.03 (d, J = 8.4Hz, 2H), 6.86 (dd, J = 8.4Hz, J = 2.4Hz, 1H), 6.81 (d, J = 2.4Hz, 1H), 6.77 (d, J = 8. 4Hz,2H),4.23(q,J=7.1Hz,2H),3.97–3.85(m,4H),3.74(s,3H),2.57(t,J =7.8Hz,2H).,2.29–2.21(m,1H),2.12–2.02(m,1H),1.25(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.5 (t, J = 33.0Hz), 163.1, 161.9, 158.1, 155.2, 142.0, 132.9, 129.3, 129.2, 119.7 (d, J = 5.7Hz), 115.9 (t,J=256.0Hz),113.9,112.9,112.7,100.6,63.2,55.9(d,J=4.3Hz),55.3(d,J=4.0Hz),42.0(t,J=22.7Hz),32.2,29.9,14.0. 19 F NMR (376MHz, CDCl3) δ-108.11 (dd, J=252.7Hz, J=12.8Hz, 1F), -111.58 (dd, J=253.0Hz, J=18.4Hz, 1F). HRMS (ESI): calculated for C 24 H 25 O6F2([M+H) + ):447.1614; Found:447.1613.C-7 is a new compound.

[0065] Example 18

[0066]

[0067] To a 25 mL reaction tube, 419.6 mg (1.6 mmol, 8 equiv) of B-8 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-8 in 86% yield, while B-8 was recovered in 65% yield. 1 H NMR (400MHz, CDCl3) δ7.67(s,1H),7.39(d,J=8.4Hz,1H),7.02(d,J=8.4Hz,2H),6.86(d t,J=8.8Hz,J=2.8Hz,1H),6.76(d,J=8.0Hz,2H),6.72(t,J=3.2Hz,1H),4.79(q,J=6.8H z,1H),4.23(qd,J=7.1Hz,J=2.8Hz,4H),3.94–3.84(m,1H),3.73(s,3H),2.55(t,J=7.8 Hz,2H),2.28–2.19(m,1H),2.11–2.01(m,1H),1.66(d,J=7.2Hz,3H),1.30–1.22(m,6H). 13 C NMR (101MHz, CDCl3) δ171.2 (d, J = 1.4Hz), 163.4 (t, J = 32.9Hz), 161.7 (d, J = 2.7Hz), 1 60.8,158.0,154.8,141.8,132.8,129.4,129.3,120.1(d,J=5.4Hz),115.8(t,J=260. 0Hz),113.9,113.3(d,J=11.7Hz),113.2(d,J=1.5Hz),101.5(d,J=12.1Hz),72.8(d,J =2.9Hz),63.2,61.8,55.2,42.2–41.6(m),32.0(d,J=3.3Hz),29.8,18.4,14.3,13.8. 19 F NMR (376MHz, CDCl3) δ-108.79 (ddd, J=253.4Hz, J=45.1Hz, J=13.9Hz, 1F), -112.01 (dm, J=252.7Hz, 1F). HRMS (ESI): calculated for C 28 H 31 O8F2([M+H] +):533.1982; Found:533.1978.C-8 is a new compound.

[0068] Example 19

[0069]

[0070] To a 25 mL reaction tube, 488.6 mg (2.0 mmol, 10.0 equiv) of B-9 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-9 with a yield of 45%, while B-9 was recovered in 73% yield. 1 H NMR (400MHz, CDCl3) δ7.65 (s, 1H), 7.30 (d, J = 8.8Hz, 1H), 7.04 (d, J = 8.8Hz, 2H), 6. 85(d,J=8.8Hz,1H),6.78(d,J=8.8Hz,2H),5.24–5.21(m,1H),4.23(q,J=8.2Hz,2H) ,3.98–3.87(m,4H),3.74(s,3H),3.53(d,J=7.2Hz,2H),2.57(t,J=7.8Hz,2H).,2.2 9–2.21(m,1H),2.12–2.00(m,1H),1.84(s,3H),1.68(s,3H),1.23(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.6 (t, J = 33.0Hz), 161.9, 160.4, 158.0, 152.1, 142.3 (d, J = 6.8Hz), 133.0, 132. 8,129.3(d,J=12.9Hz),126.7(d,J=13.7Hz),121.1(d,J=16.7Hz),119.5(d,J=5.8Hz),117.3,116.0(t, J=255.9Hz),113.9(d,J=5.1Hz),113,1,107.7(d,J=9.5Hz),63.1,56.2(d,J=16.1Hz),55.2(d,J=13.5H z),42.3–41.7(m),32.1,29.9,25.9(d,J=8.4Hz),22.1–22.0(m),18.0(d,J=5.9Hz),13.8(d,J=5.9Hz). 19F NMR (376MHz, CDCl3) δ-107.36 (d, J=253.0Hz, 1F), -111.36 (d, J=252.7Hz, 1F). HRMS (ESI): calculated for C 29 H 33 O6F2([M+H) + ):515.2240;Found:515.2236.C-9 is a new compound.

[0071] Example 20

[0072]

[0073] To a 25 mL reaction tube, 232.3 mg (1.6 mmol, 8 equiv) of B-10 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-10 with a yield of 67%, and B-10 was recovered in 78% yield. 1 H NMR (400MHz, CDCl3) δ13.0 (s, 1H), 7.94 (s, 1H), 7.62 (d, J = 7.6Hz, 1H), 7.59–7. 56(m,1H),7.49(d,J=8.4Hz,1H),7.27(t,J=7.0Hz,1H),7.09(d,J=8.8Hz,2H),6 .79(d,J=8.4Hz,2H),4.39-4.28(m,1H),4.20(q,J=7.2Hz,2H),3.74(s,3H),2.6 2(t,J=7.8Hz,2H),2.42–2.34(m,1H),2.26–2.16(m,1H),1.18(t,J=7.2Hz,3H). 13C NMR(101MHz, CDCl3)δ164.3,163.9(t,J=32.9Hz),158.0,139.6,138.0,133.3,13 0.9(d,J=5.2Hz),129.4(d,J=12.7Hz),128.1(d,J=6.9Hz),127.6(d,J=5.0Hz),1 22.9(d,J=12.5Hz),119.8,116.4(t,J=255.4Hz),116.0(d,J=8.7Hz),113.8(d,J =5.8Hz), 62.9, 55.3 (d, J = 13.4Hz), 41.0–40.5 (m), 32.1, 30.2, 13.8 (d, J = 4.7Hz). 19 F NMR (376MHz, CDCl3) δ-107.10 (dd, J=251.5Hz, J=12.4Hz, 1F), -111.89 (dd, J=251.9Hz, J=19.6Hz, 1F). HRMS (ESI): calculated for C 23 H 24 O4NF2([M+H) + ):416.1668; Found:416.1667.C-10 is a new compound.

[0074] Example 21

[0075]

[0076] To a 25 mL reaction tube, 257.9 mg (1.6 mmol, 8 equiv) of B-11 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation to give compound C-11 in 45% yield. B-11 was recovered in 85% yield. mp: 188–190 °C 1H NMR (400MHz, CDCl3) δ11.7(s,1H),10.2(s,1H),7.87(s,1H),7.54(d,J=8.4Hz,1 H),7.04(d,J=8.4Hz,2H),6.78(d,J=8.8Hz,2H),6.73(d,J=2.0Hz,1H),6.67(dd ,J=8.0Hz,J=2.4Hz,1H),4.15(q,J=6.5Hz,2H),3.97–3.86(m,1H),3.68(s,3H), 2.50–2.44(m,1H),2.38–2.30(m,1H),2.16–2.02(m,2H),1.10(t,J=7.2Hz,3H). 13 CNMR(101MHz,DMSO-d6)δ163.3(t,J=32.9Hz),162.3,160.0,157.6,140.2,138.7,132.9,129.8,129. 4,122.1(d,J=4.6Hz),116.5(t,J=254.3Hz),113.7,112.5,112.0,99.6,62.8,55.0,31.4,39.0,13.6. 19 F NMR(376MHz, DMSO-d6)δ-108.26(d,J=247.8Hz,1F),-112.43(d,J=250.0Hz,1F).HRMS(ESI):calculated for C 23 H 24 O5NF2([M+H) + ):432.1617; Found:432.1618.C-11 is a new compound.

[0077] Example 22

[0078]

[0079] To a 25 mL reaction tube, 261.0 mg (1.6 mmol, 8 equiv) of B-12 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-12 with a yield of 49%, and B-12 was recovered in 72% yield. 1H NMR (400MHz, CDCl3) δ13.21(s,1H),7.88(s,1H),7.47–7.44(m,1H),7.35–7.29(m,2H),7.07(d,J=8.4Hz,2H),6.78(d,J=8.4Hz,2H),4. 37–4.25(m,1H),4.20(q,J=7.2Hz,2H),3.74(s,3H),2.60(t,J=7.8Hz,2H),2.41–2.32(m,1H),2.23–2.13(m,1H),1.19(t,J=7.0Hz,3H). 13 C NMR(101MHz, CDCl3)δ164.0,163.8(t,J=32.9Hz),159.5,158.0,157.1,138 .8,134.5,133.1,129.4(d,J=15.9Hz),120.4(d,J=9.0Hz),119.5–119.1(m) ,117.9–117.5(m),116.2(t,J=256.1Hz),113.9(d,J=7.1Hz),113.0–112.6( m), 63.0, 55.2 (d, J = 14.6Hz), 41.0–40.4 (m), 32.1, 30.1, 13.8 (d, J = 6.2Hz). 19 F NMR(376MHz, CDCl3)δ-107.92(dd,J=252.7Hz,J=13.2Hz,1F),-111.96(dd,J=252.3Hz,J=19.5Hz,1F),-119.78--119.84(m,1F).HRMS(ESI):calculated for C 23 H 23 O4NF3([M+H) + ):434.1574; Found:434.1569.C-12 is a new compound.

[0080] Example 23

[0081]

[0082] To a 25 mL reaction tube, 287.4 mg (1.6 mmol, 8 equiv) of B-13 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. After stirring at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation, compound C-13 was obtained with a yield of 41%, and B-13 was recovered in 83% yield. mp: 137–139 °C 1 H NMR (400MHz, CDCl3) δ13.12 (s, 1H), 7.85 (s, 1H), 7.60 (d, J = 2.4Hz, 1H), 7.50 ( dd,J=8.8Hz,J=2.4Hz,1H),7.40(d,J=8.8Hz,1H),7.06(d,J=8.4Hz,2H),6.77 (d,J=8.4Hz,2H),4.35–4.27(m,1H),4.20(q,J=7.1Hz,2H),3.74(s,3H),2.59 (t,J=7.8Hz,2H),2.40–2.31(m,1H),2.22–2.12(m,1H),1.19(t,J=7.2Hz,3H). 13 C NMR(101MHz, CDCl3) δ164.1,163.8(t,J=33.0Hz),158.0,138.5,136.4,133.0,131.1,129.4,129.0,128.2,127 .2,120.7,117.5,116.2(t,J=256.1Hz),113.9,63.0,55.3(d,J=3.1Hz),40.7(t,J=22.4Hz),32.1,30.1,13.9. 19 F NMR (376MHz, CDCl3) δ-108.11 (d, J=251.9Hz, 1F), -111.92 (d, J=253.4Hz, 1F). HRMS (ESI): calculated for C 23 H 23 O4NClF2([M+H) + ):450.1278; Found:450.1276.C-13 is a new compound.

[0083] Example 24

[0084]

[0085] To a 25 mL reaction tube, 179.2 mg (0.8 mmol, 4 equiv) of B-14 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation to give compound C-14 in 48% yield. B-14 was recovered in 80% yield. mp: 139–141 °C 1 H NMR (400MHz, CDCl3) δ13.14(s,1H),7.84(s,1H),7.76(d,J=2.4Hz,1H),7.63( dd,J=8.8Hz,J=2.4Hz,1H),7.34(d,J=8.4Hz,1H),7.05(d,J=8.4Hz,2H),6.77 (d,J=8.4Hz,2H),4.34–4.27(m,1H),4.20(q,J=7.8Hz,2H),3.74(s,3H),2.59 (t,J=7.6Hz,2H),2.40–2.31(m,1H),2.21–2.12(m,1H),1.19(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ164.1,163.7(t,J=32.6Hz),158.1,138.4,136.7,133.8,133.0,130.3,129.4,129.0(d,J=5.1H z), 121.2, 117.7, 116.2 (t, J = 256.3Hz), 115.5, 113.9, 63.0, 55.3 (d, J = 5.8Hz), 40.7 (t, J = 22.2Hz), 32.1, 30.1, 13.9. 19 F NMR (376MHz, CDCl3) δ-107.46 (dd, J=252.7Hz, J=13.2Hz, 1F), -111.26 (dd, J=252.3Hz, J=19.2Hz, 1F). HRMS (ESI): calculated for C 23 H 23 O4NBrF2([M+H) + ):494.0773; Found:494.0771.C-14 is a new compound.

[0086] Example 25

[0087]

[0088] To a 25 mL reaction tube, 254.7 mg (1.6 mmol, 8 equiv) of B-15 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. After stirring at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation, compound C-15 was obtained with a yield of 52%, and B-15 was recovered in 65% yield. mp: 75–77 °C 1 H NMR (400MHz, CDCl3) δ7.78(s,1H),7.60–7.57(m,2H),7.35(d,J=8.8Hz,1H),7.26(t,J=7.6Hz,1H),7.04(d,J=8.4Hz,2H),6.77(d,J=8.8Hz,2H),4 .36–4.27(m,1H),4.23(q,J=7.1Hz,2H),3.76(s,3H),3.74(s,3H),2.62– 2.48(m,2H),2.32–2.24(m,1H),2.15–2.07(m,1H),1.21(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.8(t,J=32.8Hz),162.2,157.9,139.4,137.8,133.4,130.9,129.3,129.2,127.7(d,J=5 .2Hz),122.4,120.2,116.3(t,J=251.0Hz),114.1,113.8,62.9,55.3,41.6(t,J=22.5Hz),32.3,30.4,30.3,13.9. 19 F NMR (376MHz, CDCl3) δ-107.85 (dd, J=252.7Hz, J=9.0Hz, 1F), -111.09 (dd, J=252.3Hz, J=19.2Hz, 1F). HRMS (ESI): calculated for C 24 H 26 O4NF2([M+H) + ):430.1824; Found:430.1826.C-15 is a new compound.

[0089] Example 26

[0090]

[0091] To a 25 mL reaction tube, 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine was added. After purging with argon three times, 1.0 mL of DMSO, 174.6 mg (1.6 mmol, 8 equiv) of B-16, and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-16 in 61% yield, while B-16 was recovered in 64% yield. 1 H NMR (400MHz, CDCl3) δ7.44(d,J=6.8Hz,1H),7.27–7.24(m,1H),7.04(d,J=8.4Hz,2H),6.79(d,J=8.8Hz,2H),6.19(t,J=7.0Hz,1H),4.21(q, J=7.2Hz,2H),4.17–4.01(m,1H),3.76(s,3H),3.56(s,3H),2.56–2.42(m,2H),2.22–2.13(m,1H),2.02–1.92(m,1H),1.22(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.9 (t, J = 33.1Hz), 162.9, 157.9, 138.1, 137.7, 133.5, 129.3, 126.9 (d, J = 5 .4Hz), 116.4 (t, J=249.7Hz), 113.8, 105.6, 62.8, 55.3, 41.2 (t, J=22.4Hz), 38.4, 32.2, 30.3, 13.9. 19 F NMR (376MHz, CDCl3) δ-108.16 (d, J=251.2Hz, 1F), -111.49 (dd, J=251.5Hz, J=19.2Hz, 1F). HRMS (ESI): calculated for C 20 H 24 O4NF2([M+H) + ):380.1668; Found:380.1667.C-16 is a new compound.

[0092] Example 27

[0093]

[0094] To a 25 mL reaction tube, 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine was added. After purging with argon three times, 1.0 mL of B-17 and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-17 in 48% yield. 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.0Hz,1H),7.33(d,J=8.0Hz,1H),7.24(t,J=7 .4Hz,1H),7.13(t,J=7.4Hz,1H),6.98(d,J=8.4Hz,2H),6.82(d,J=8.4Hz,2H),6 .57(s,1H),4.15(q,J=7.1Hz,2H),3.80(s,3H),3.71–3.62(m,1H),3.59(s,3H), 2.70–2.63(m,1H),2.49–2.42(m,1H),2.37–2.21(m,2H),1.10(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.9 (t, J = 32.8Hz), 158.2, 137.5, 134.1 (d, J = 5.7Hz), 132.6, 129.4, 127.8, 121.7, 120 .7,119.7,116.0(t,J=256.9Hz),114.0,109.5,101.9,63.0,55.4,40.5(t,J=24.0Hz),31.7,30.3,29.8,13.8. 19 F NMR (376MHz, CDCl3) δ-106.79 (d, J=252.3Hz, 1F), -110.49 (dd, J=256.1Hz, J=15.4Hz, 1F). HRMS (ESI): calculated for C 23 H 26 O3NF2([M+H) + ):402.1875; Found:402.1876.C-17 is a new compound.

[0095] Example 28

[0096]

[0097] To a 25 mL reaction tube, 420.1 mg (2.0 mmol, 10 equiv) of B-18 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 48 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-18 in 35% yield, while B-18 was recovered in 75% yield. 1 H NMR (400MHz, CDCl3) δ7.72(d,J=1.6Hz,1H),7.72(dd,J=8.4Hz,J=1.6Hz,1H),7.18(d,J=8.8Hz,1H),6.95(d,J=8.4Hz,2H),6.81(d,J=8.8Hz,2H),6.49(s ,1H),4.15(q,J=7.1Hz,2H),3.79(s,3H),3.67–3.56(m,1H),3.54(s,3H),2. 68–2.62(m,1H),2.47–2.39(m,1H),2.36–2.18(m,2H),1.11(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.8 (t, J = 32.7Hz), 158.2, 136.2, 135.4 (d, J = 5.8Hz), 132.3, 129.4, 129.3, 124.6-124.5 (m), 123.0 (d, J = 3.2Hz), 115.8 (t ,J=256.9Hz),114.0,113.0,111.0-110.9(m),101.4,63.0,55.4(d,J=10 .0Hz),40.7-40.3(m),31.6,30.0(d,J=3.0Hz),29.9(d,J=4.5Hz),13.9. 19 F NMR (376MHz, CDCl3) δ-107.02 (dd, J=256.8Hz, J=11.3Hz, 1F), -110.25 (dd, J=256.8Hz, J=15.0Hz, 1F). HRMS (ESI): calculated for C 23 H 25 O3NBrF2([M+H) + ):480.0980; Found:480.0979.C-18 is a new compound.

[0098] Example 29

[0099]

[0100] To a 25 mL reaction tube, 257.9 mg (1.6 mmol, 8 equiv) of B-19 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 70.2 mg (0.2 mmol, 1 equiv) of compound A-1 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-19 with a yield of 37%, while B-19 was recovered in 77% yield. 1 H NMR (400MHz, CDCl3) δ7.26–7.22(m,1H),7.10(d,J=2.0Hz,1H),6.99(d,J=8.0H z,2H),6.92(dd,J=8.8Hz,J=2.4Hz,1H),6.84(d,J=8.8Hz,2H),6.51(s,1H),4. 16(q,J=6.9Hz,2H),3.88(s,3H),3.81(s,3H),3.74–3.61(m,1H),3.56(s,3H), 2.71–2.65(m,1H),2.50–2.43(m,1H),2.37–2.22(m,2H),1.11(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.9(t,J=32.8Hz),158.1,154.2,134.4(d,J=5.8Hz),132.9,132.1,129.4,128.0,115.9(t,J=256.6Hz ),114.0,112.0,110.2,102.1,101.4,62.9,55.9(d,J=4.8Hz),55.3(d,J=4.8Hz),40.5(t,J=22.7Hz),31.7,30.2,29.9,13.8. 19 F NMR (376MHz, CDCl3) δ-106.60 (dd, J=254.9Hz, J=13.9Hz, 1F), -111.39 (dd, J=254.5Hz, J=16.5Hz, 1F). HRMS (ESI): calculated for C 24 H 28 O4NF2([M+H) + ):432.1981; Found:432.1983.C-19 is a new compound.

[0101] Example 30

[0102]

[0103] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 76.2 mg (0.2 mmol, 1 equiv) of compound A-2 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm), compound C-20 was obtained with a yield of 78% and a coumarin recovery rate of 81%. mp: 83–85 °C 1 H NMR (400MHz, CDCl3) δ7.72(s,1H),7.53(t,J=8.6Hz,1H),7.47(d,J=7.6Hz,1H),7.33–7.26(m,2H),6.70(d,J=8.4Hz,1H),6.64(d,J=6.8Hz,2H),4.2 2(q,J=7.2Hz,2H),4.02–3.91(m,1H),3.84(s,3H),3.77(s,3H),2.59(t,J =7.6Hz,2H),2.32–2.24(m,1H),2.17–2.08(m,1H),1.23(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4(t,J=32.9Hz),161.5,153.2,148.8,147.4,141.9,133.2,132.1,128.1,124.7,123.6(d,J=5 .5Hz),120.2,118.9,116.6,115.7(t,J=256.1Hz),111.6,111.2,77.4,63.2,55.9,41.9(t,J=23.0Hz),32.6,29.8,13.8. 19 F NMR(376MHz, CDCl3)δ-108.17(dm,J=253.4Hz,1F),-111.33(dt,J=253.4Hz,J=10.5Hz,1F).HRMS(ESI):calculated forC 24 H 25 O6F2([M+H) + ):447.1614; Found:447.1613.C-20 is a new compound.

[0104] Example 31

[0105]

[0106] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 71.2 mg (0.2 mmol, 1 equiv) of compound A-3 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm) irradiation, compound C-21 was obtained with a yield of 72%, and coumarin recovery was 77%. mp: 73–75 °C 1 H NMR (400MHz, CDCl3) δ7.72 (s, 1H), 7.57–7.53 (m, 1H), 7.50 (dd, J=7.6Hz, J=1.6Hz, 1H ),7.34–7.28(m,2H),6.66(d,J=8.0Hz,1H),6.60(d,J=1.6Hz,1H),6.55(dd,J=8.0Hz ,J=1.6Hz,1H),5.84(dd,J=7.2Hz,J=1.6Hz,2H),4.25(q,J=7.1Hz,2H),4.01–3.89(m ,1H),2.62–2.51(m,2H),2.31–2.23(m,1H),2.13–2.03(m,1H),1.26(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4(t,J=32.8Hz),161.5,153.3,147.8,146.0,141.9,134.5,132.1,128.2,124.7,123.6(d,J =5.1Hz),121.3,118.9,116.7,115.7(t,J=255.8Hz),108.7,108.4,100.9,63.3,42.0(t,J=22.9Hz),32.9,29.9,13.9. 19 F NMR (376MHz, CDCl3) δ-108.72 (dd, J=253.8Hz, J=13.2Hz, 1F), -111.99 (dd, J=253.4Hz, J=18.8Hz, 1F). HRMS (ESI): calculated for C 23 H 21 O6F2([M+H) + ):431.1301; Found:431.1298.C-21 is a new compound.

[0107] Example 32

[0108]

[0109] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 81.0 mg (0.2 mmol, 1 equiv) of compound A-4 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm), compound C-22 was obtained with a yield of 72% and a 78% recovery rate of coumarin. mp: 62–64 °C 1 H NMR (400MHz, CDCl3) δ7.77(s,1H),7.57–7.53(m,1H),7.50(dd,J=7.6Hz,J=1.6Hz,1H),7.35–7.29(m,2H),7.15(d,J=8.4Hz,2H),7.08(d,J =8.4Hz,2H),4.24(q,J=7.1Hz,2H),4.04–3.92(m,1H),2.65(t,J=7.8Hz,2H),2.35–2.27(m,1H),2.17–2.07(m,1H),1.24(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.3(t,J=32.7Hz),161.5,153.3,147.7(q,J=1.9Hz),142.0,139.5,132.3,129.7,128.3,124.8,123.6(d,J= 5.5Hz), 121.2, 120.5 (q, J = 260.9Hz), 118.9, 116.7, 115.7 (t, J = 256.3Hz), 63.4, 42.1 (t, J = 23.0Hz), 32.4, 29.8 (t, J = 2.9Hz), 13.9. 19 F NMR (376MHz, CDCl3) δ-58.02 (d, J=7.4Hz, 3F), -107.76 (dm, J=254.9Hz, 1F), -111.45 (dm, J=254.9Hz, 1F). HRMS (ESI): calculated for C 23 H 20 O5F5([M+H) + ):471.1225; Found:471.1224.C-22 is a new compound.

[0110] Example 33

[0111]

[0112] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 64.2 mg (0.2 mmol, 1 equiv) of compound A-5 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm) irradiation, compound C-23 was obtained with a yield of 74%, and coumarin recovery was 76%. mp: 100–102 °C 1 H NMR(400MHz, CDCl3)δ7.76(s,1H),7.54(t,J=8.6Hz,1H),7.50(d,J=8.0Hz,1H),7.34–7.22(m,4H),7.16–7.12(m,3H),4.2 4(q,J=7.2Hz,2H),4.05–3.93(m,1H),2.64(t,J=8.0Hz,2H),2.36–2.27(m,1H),2.19–2.09(m,1H),1.25(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4 (t, J = 32.9Hz), 161.5, 153.3, 141.9, 140.8, 132.1, 128.6, 128.4, 128.2, 126.3, 124.7, 123.7 (d, J = 5.7Hz), 119.0, 116.7, 115.8 (t, J = 256.2Hz), 63.3, 42.2 (t, J = 22.9Hz), 33.1, 29.7, 13.9. 19 F NMR (376MHz, CDCl3) δ-108.15 (dd, J=254.2Hz, J=13.2Hz, 1F), -111.18 (dd, J=254.2Hz, J=18.4Hz, 1F). HRMS (ESI): calculated for C 22 H 21 O4F2([M+H) + ):387.1402; Found:387.1403.C-23 is a new compound.

[0113] Example 34

[0114]

[0115] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 67.0 mg (0.2 mmol, 1 equiv) of compound A-6 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm), compound C-24 was obtained with a yield of 73% and a 78% recovery of coumarin. mp: 70–72 °C 1 H NMR (400MHz, CDCl3) δ7.74(s,1H),7.54(t,J=8.6Hz,1H),7.49(dd,J=7.6Hz,J=1.6Hz,1H),7.34–7.26(m,2H),7.03(q,J=7.1Hz,4H),4. 25(q,J=7.2Hz,2H),4.04–3.92(m,1H),2.62(t,J=8.6Hz,2H),2.36–2.26(m,1H),2.24(s,3H),2.18–2.09(m,1H),1.26(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.4 (t, J = 32.8Hz), 161.5, 153.3, 141.9, 137.7, 135.9, 132.0, 129.3, 128.2, 128.2, 124 .7,123.7(d,J=5.6Hz),119.0,116.6,115.8(t,J=256.1Hz),63.3,42.2(t,J=22.8Hz),32.7,29.7,21.0,13.9. 19 F NMR (376MHz, CDCl3) δ-108.15 (dd, J=254.2Hz, J=13.2Hz, 1F), -111.18 (dd, J=254.2Hz, J=18.4Hz, 1F). HRMS (ESI): calculated for C 23 H 23 O4F2([M+H) + ):401.1559; Found:401.1558.C-24 is a new compound.

[0116] Example 35

[0117]

[0118] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 75.4 mg (0.2 mmol, 1 equiv) of compound A-7 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-25 with a yield of 67% and a coumarin recovery rate of 83%. 1 H NMR (400MHz, CDCl3) δ7.74(s,1H),7.56–7.52(m,1H),7.49(dd,J=9.2Hz,J=1.6Hz,1H),7.34–7.25(m,4H),7.07(d,J=8.0Hz, 2H),4.25(q,J=7.2Hz,2H),4.07–3.96(m,1H),2.71–2.57(m,2H),2.37–2.29(m,1H),2.19–2.09(m,1H),1.28–1.25(m,12H). 13 CNMR (101MHz, CDCl3) δ163.4 (t, J = 32.9Hz), 161.5, 153.3, 149.1, 141.8, 137.7, 132.0, 128.2, 128.0, 125.5, 124.7, 123. 7(d,J=5.2Hz),118.9,116.6,115.8(t,J=256.2Hz),63.3,42.2(t,J=22.9Hz),34.4,32.6,31.4,29.6(t,J=3.1Hz),13.9. 19 F NMR (376MHz, CDCl3) δ-108.42 (dm, J=254.2Hz, 1F), -111.16 (dm, J=253.4Hz, 1F). HRMS (ESI): calculated for C 26 H 29 O4F2([M+H) + ):443.2028; Found:443.2027.C-25 is a new compound.

[0119] Example 36

[0120]

[0121] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 77.8 mg (0.2 mmol, 1 equiv) of compound A-8 were added. After stirring at 30 °C for 48 h under ultraviolet light (410–415 nm), compound C-26 was obtained with a yield of 75% and a 77% recovery of coumarin. mp: 64–66 °C 1 H NMR (400MHz, CDCl3) δ7.76 (s, 1H), 7.58–7.53 (m, 1H), 7.50–7.47 (m, 3H), 7.34–7.29 (m, 2H), 7.25 (d, J = 8.4Hz, 2H), 4.2 4(q,J=7.2Hz,2H),4.04–3.93(m,1H),2.74–2.69(m,2H),2.38–2.30(m,1H),2.20–2.10(m,1H),1.24(t,J=7.2Hz,3H). 13 CNMR(101MHz, CDCl3)δ163.3(t,J=32.8Hz),161.5,153.3,144.9,142.0,132.3,128.8,128.7(q,J=32.6Hz),128.2,125.5(q,J=3.8Hz ), 124.8, 124.3 (q, J = 260.5Hz), 123.5 (d, J = 5.8Hz), 118.8, 116.7, 115.7 (t, J = 256.4Hz), 63.4, 42.1 (t, J = 23.0Hz), 33.0, 29.6, 13.9. 19 FNMR(376MHz, CDCl3)δ–63.04(s,3F),-108.13(dd,J=254.9Hz,J=13.2Hz,1F),-112.13(dd,J=255.3Hz,J=18.8Hz,1F).HRMS(ESI):calculated for C 23 H 20 O4F5([M+H) + ):455.1276; Found:455.1272.C-26 is a new compound.

[0122] Example 37

[0123]

[0124] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 79.4 mg (0.2 mmol, 1 equiv) of compound A-9 were added. The mixture was stirred at 30 °C for 12 h under ultraviolet light (410-415 nm) irradiation to obtain compound C-27 in 80% yield, with 85% recovery of coumarin. 1 H NMR(400MHz, CDCl3)δ7.65(s,1H),7.56–7.52(m,1H),7.44(dd,J=7.6Hz,J=1.6Hz,1H),7.33–7.28(m,4H),7.24–7.18(m,7H),7.0 8–7.03(m,1H),4.21(qd,J=7.2Hz,J=2.0Hz,2H),3.89–3.78(m,2H),2.82–2.75(m,1H),2.69–2.61(m,1H),1.21(t,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ163.3 (t, J = 32.8Hz), 161.1, 153.4, 144.1, 142.9, 142.4 ( d,J=2.9Hz),132.1,128.8(d,J=2.7Hz),128.6(d,J=1.7Hz),128.2(m),128.0,1 27.6,126.9,126.5,124.6(d,J=1.8Hz),123.2(d,J=4.3Hz),118.9,116.6,115 .8(t,J=256.2Hz),63.3,48.6(m),41.8(t,J=23.4Hz),33.6,13.8(d,J=1.7Hz). 19 F NMR (376MHz, CDCl3) δ-108.01 (d, J=253.0Hz, 1F), -109.67 (d, J=252.3Hz, 1F). HRMS (ESI): calculated for C 28 H 25 O4F2([M+H) + ):463.1715; Found:463.1711.C-27 is a new compound.

[0125] Example 38

[0126]

[0127] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 73.0 mg (0.2 mmol, 1 equiv) of compound A-10 were added. After stirring at 30 °C for 48 h under ultraviolet light (410–415 nm) irradiation, compound C-28 was obtained with a yield of 60% and a 68% recovery rate of coumarin. mp: 122–124 °C 1 H NMR (400MHz, CDCl3) δ7.77(s,1H),7.55–7.51(m,2H),7.34–7.27(m,2H),4.28(q,J=7.2Hz,2H),4.14–4.03 (m,1H),1.89(s,3H),1.72(d,J=14.4Hz,1H),1.66–1.54(m,7H),1.48(d,J=11.6Hz,3H),1.35–1.29(m,6H). 13 C NMR (101MHz, CDCl3) δ163.6 (t, J = 33.1Hz), 161.5, 153.3, 141.8, 131.9, 128.2, 126.1, 124.6, 11 9.1,116.7,116.3(t,J=256.0Hz),63.3,43.1,42.6,36.8,36.7(t,J=24.0Hz),32.8,28.5,14.0. 19 FNMR(376MHz,CDCl3)δ-110.12(m,2F).HRMS(ESI):calculated for C 25 H 29 O4F2([M+H) + ):431.2028; Found:431.2025.C-28 is a new compound.

[0128] Example 39

[0129]

[0130] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 62.6 mg (0.2 mmol, 1 equiv) of compound A-11 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm), compound C-29 was obtained with a yield of 77% and a coumarin recovery rate of 80%. mp: 102–104 °C1 H NMR(400MHz, CDCl3)δ7.73(s,1H),7.55–7.50(m,2H),7.32–7.26(m,2H),4.33–4.21(m,2H),4.13–4.01(m,1H),1.84( d,J=12.4Hz,1H),1.79–1.57(m,6H),1.28(t,J=7.2Hz,3H),1.20–1.05(m,4H),1.00–0.90(m,1H),0.88–0.78(m,1H). 13 CNMR(101MHz, CDCl3)δ163.6(t,J=33.0Hz),161.5,153.2,141.8,131.9(d,J=2.7Hz),128.2,124.7–124.6(m),124.1(d,J=4.9Hz) ,119.0,116.7–116.5(m),116.0(t,J=256.0Hz),63.2,39.6–39.0(m),35.4,34.5,34.3,32.0,26.4,26.2,25.9,13.9(d,J=3.4Hz). 19 F NMR (376MHz, CDCl3) δ-109.71 (dd, J=253.0Hz, J=14.7Hz, 1F), -111.02 (dd, J=252.7Hz, J=17.7Hz, 1F). HRMS (ESI): calculated for C 21 H 24 O4F2([M] + ):378.1637; Found:378.1633.C-29 is a new compound.

[0131] Example 40

[0132]

[0133] To a 25 mL reaction tube, 233.8 mg (1.6 mmol, 8 equiv) of B-1 and 48.9 mg (0.4 mmol, 2 equiv) of 4-dimethylaminopyridine were added. After purging with argon three times, 1.0 mL of DMSO and 63.0 mg (0.2 mmol, 1 equiv) of compound A-12 were added. After stirring at 30 °C for 12 h under ultraviolet light (410–415 nm) irradiation, compound C-30 was obtained with a yield of 82% and a coumarin recovery rate of 87%. mp: 113–115 °C 1H NMR(400MHz, CDCl3)δ7.76(s,1H),7.57–7.51(m,2H),7.34–7.29(m,2H),4.31–4.23(m,2H) ,4.14–4.02(m,1H),3.94–3.86(m,2H),3.26(m,2H),1.84–1.76(m,3H),1.51–1.17(m,7H). 13 C NMR (101MHz, CDCl3) δ163.4(t,J=32.9Hz),161.5,153.2,142.0,132.2,128.3,124.8,123.9(d,J=5.6Hz),118.9 ,116.7,115.9(t,J=256.1Hz),67.7(d,J=2.9Hz),63.3,38.8(t,J=22.6Hz),35.3,33.8,32.0(d,J=6.6Hz),14.0. 19 FNMR (376MHz, CDCl3) δ-108.82 (dd, J=254.2Hz, J=13.5Hz, 1F), -111.59 (dd, J=254.2Hz, J=18.0Hz, 1F). HRMS (ESI): calculated for C 20 H 23 O5F2([M+H) + ):381.1508; Found:381.1504.C-30 is a new compound.

[0134] Compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, and C-30 synthesized in Examples 1-40 are all new compounds with potential applications in pesticides, materials, and molecular imaging.

[0135] Application examples

[0136] Activity testing of coupling products of ethyl 3-bromo-3-alkyl-2,2-difluoropropionate and coumarin, quinolinone, and indole.

[0137] Cell lines and solvents: Human hepatocellular carcinoma Huh-7 cells; human lung cancer A549 cells; cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum; solvent: dimethyl sulfoxide (DMSO).

[0138] CCK-8 staining method for detecting antitumor cell activity: implementation plan

[0139] Cells with a viable cell percentage of over 90% were selected for the experiment. The cell proliferation inhibition assay used the EnoGeneCell™ Counting Kit-8 (CCK-8) cell viability assay kit. Human hepatocellular carcinoma Huh-7 cells and human lung cancer A549 cells in logarithmic growth phase were collected, culture medium discarded, washed twice with PBS, trypsinized, centrifuged, and resuspended in culture medium. Cells were then incubated at 5 × 10⁻⁶ cells / day. 4 Each well was seeded with one sample of the test compound in parallel. The 96-well plates were incubated at 37°C in a 5% CO2 incubator for 8 hours. Afterward, 4 μM of the test compound's culture medium was added to each well. A negative control group, a solvent control group, and a positive control group were also established (positive controls were sorafenib and cisplatin, respectively). Each group was divided into three replicates. After further incubation at 37°C in a 5% CO2 incubator for 48 hours, 10 μL of CCK-8 solution was added to each well. The culture plates were incubated in the incubator, and the absorbance (OD value) at 450 nm was measured using a microplate reader. Both the experimental and control groups were repeated three times. The inhibition rate of each compound on the proliferation of human liver cancer cells (Huh-7) and human lung cells (A549) was calculated. The experimental results are detailed in Table 1.

[0140] Table 1: Inhibition rate of proliferation of human hepatocellular carcinoma Huh-7 cells and human lung cancer A549 cells

[0141] C-11 33 37 C-17 43 49 C-19 36 38 Soraphine 30 — Cisplatin — 38

[0142] The experimental results in Table 1 show that compounds C-11, C-17, and C-19 of this invention exhibit significant in vitro antitumor activity. The three compounds showed relatively significant inhibitory activity against human hepatocellular carcinoma cells (Huh-7) and human lung cancer cells (A549). Therefore, compounds C-11, C-17, and C-19 are suitable antitumor drug candidates.

[0143] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific structures and characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the structure of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing compound C, characterized in that: Compound C was obtained by mixing compound A with compound B at room temperature, adding DMSO as solvent, and using 4-dimethylaminopyridine as base under ultraviolet light irradiation at 410-415 nm. The specific reaction formula is as follows: ， In the above formulas, R1 is selected from C1-12 alkyl, phenyl and alkyl or halogen-substituted phenyl groups, and R2 is selected from H, C1-6 alkyl, phenyl, alkenyl, ester, hydroxyl or halogen substituents.

2. The method according to claim 1, characterized in that: The molar ratio of compound A to compound B is 1:1 to 10.

3. The method according to claim 1, characterized in that: The molar ratio of compound A to base is 1:

2.

4. The method according to claim 1, characterized in that: The reaction was carried out at 20℃~50℃.

5. A compound, characterized in that: The chemical formula is shown below: 。 6. The use of the compound of claim 5 in the preparation of an antitumor drug, characterized in that, The tumors were selected from liver cancer and lung cancer.

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